Clarithromycin

Clarithromycin is a macrolide antibiotic used to treat a variety of different infections. These include infections of the skin and soft tissue or the respiratory system (pharyngitis, tonsillitis, sinusitis, pneumonia).

Clarithromycin can also be used (along with other medicines) to treat the infection H. pylori in patients with duodenal ulcers.

Pharyngitis and tonsillitis caused by Streptococcus pyogenes as an alternative to first-line therapy (Penicillin by either the intramuscular or the oral route is the usual drug of choice in the treatment of Streptococcus pyogenes infection)

History of cholestatic jaundice or hepatic dysfunction associated with prior use of clarithromycin.

Coadministration with: Cisapride, pimozide, astemizole, terfenadine because of a risk for cardiac arrhythmias (QT prolongation, ventricular tachycardia, ventricular fibrillation, and torsades de pointes) most likely due to inhibition of metabolism of these drugs by clarithromycin.

Coadministration with colchicine in patients with renal or hepatic impairment

Arrhythmia: Clarithromycin should not be given to patients with history of QT prolongation or ventricular cardiac arrhythmia, including torsades de pointes

Coadministration with statins that are extensively metabolized by CYP3A4 (ie, lovastatin, simvastatin), due to the risk of myopathy, including rhabdomyolysis.

Ergot preparations (ergotamine or dihydroergotamine) should be avoided in patients who are taking clarithromycin due to inhibition of metabolism of these drugs by clarithromycin with a risk of developing clinical ergotism (i.e., hypertension, lingual ischemia, and peripheral cyanosis)[1]

Clarithromycin inhibits the hepatic microsomal CYP3A4 isoenzyme. The following are examples of some clinically significant CYP3A4 based drug interactions (Increased serum concentrations):

Carbamazepine: Blood level monitoring of carbamazepine may be considered.

Colchicine (Contraindicated)

Sildenafil, Tadalafil, or Vardenafil (Co-administration is not recommended)

Triazolam or Alprazolam: Caution and appropriate dose adjustments should be considered. For benzodiazepines which are not metabolized by CYP3A (e.g., temazepam, nitrazepam, lorazepam), a clinically important interaction with clarithromycin is unlikely.

Atazanavir: Doses of clarithromycin greater than 1000 mg per day should not be co-administered with Atazanavir

Ergotamine or dihydroergotamine: Concomitant administration of clarithromycin and ergotamine or dihydroergotamine is contraindicated, as this may result in ergot toxicity.

Antiarrhythmics: There have been post-marketing reports of torsades de pointes occurring with concurrent use of clarithromycin and quinidine or disopyramide. Electrocardiograms should be monitored for QTc prolongation during coadministration of clarithromycin with these drugs. Serum concentrations of these medications should also be monitored.

Statins: Concomitant administration of clarithromycin with lovastatin or simvastatin is contraindicated. Rhabdomyolysis have also been reported in patients taking atorvastatin or rosuvastatin concomitantly with clarithromycin. When used with clarithromycin, atorvastatin or rosuvastatin should be administered in the lowest possible doses or use of a statin that is not dependent on CYP3A metabolism (e.g. fluvastatin or pravastatin) should be considered.

Hypoglycemic agents and/or insulin: The concomitant use of clarithromycin with these drugs can result in significant hypoglycemia. With certain hypoglycemic drugs such as nateglinide, pioglitazone, repaglinide and rosiglitazone, inhibition of CYP3A enzyme by clarithromycin may be involved and could cause hypoglycemia when used concomitantly. Careful monitoring of glucose is recommended.